Background and aim: Both chronic intermittent hypoxia (CIH) and chronic continuous hypoxia (CCH) are risk factors for cardiovascular disease, which are associated with cardiac systolic function and associated with dysfunction of endothelia and coagulation-fibrinolysis system in the vasculature. However, the different effects of these two hypoxic models are not fully understood. In our study, we systemically compared the effects of CIH and CCH on cardiac function and related factor levels in serum using rat model.
Methods: Forty-five male Sprague-Dawley rats were randomly divided into the normoxia control (NC), CIH and CCH groups. The rat CIH and CCH models were established, then the blood and tissue samples were collected to analyze the function of endothelium and the coagulation-fibrinolysis system. Also, the ultrasound cardiogram was performed to directly assess myocardial contractility.
Results: Both CIH and CCH significantly decreased the NO, eNOS, P-eNOS and AT-III levels in the rat serum but significantly increased the levels of ET-1, vWF, COX-2, NF-κB, FIB, FVIII and PAI-1 in the rat serum (P < 0.05). The expression of ET-1, VWF and ICAM-1 in CIH group were higher than CCH group (P < 0.05), however, the expression of CD62p was increased in CCH group but not in CIH group. The expression of t-PA in CIH group were lower than CCH group (P < 0.05), but there were no significant differences in CCH group and NC group (P > 0.05). Using transmission electron microscope, we found that the mitochondrial ultrastructure of thoracic aorta endothelial cells in CIH and CCH group were damaged. Moreover, the myocardial contractility in CIH and CCH group were significantly decreased compared with NC group.
Conclusion: Our results suggested that CIH and CCH could cause endothelial dysfunction, dysfunction of the coagulation-fibrinolysis system and decreasing of myocardial contractility. Compared with CCH, CIH has greater effect on vasoconstriction and adhesion of vascular endothelial cells, and stronger procoagulant effect.
Keywords: Chronic intermittent hypoxia; chronic continuous hypoxia; myocardial contractility; vascular endothelial function.